The field of the present invention relates to the delivery of energy impulses (and/or fields) to bodily tissues for therapeutic purposes. It relates more specifically to the use of non-invasive devices and methods for transcutaneous electrical nerve stimulation and magnetic nerve stimulation, along with methods of treating medical disorders using energy that is delivered by such devices. The disorders comprise the following urological problems: overactive bladder, urge incontinence, stress incontinence, urge frequency, non-obstructive urinary retention and interstitial cystitis/painful bladder syndrome. In preferred embodiments of the disclosed treatment methods, one or both of the patient's posterior tibial nerves are stimulated transcutaneously near the ankle. An embodiment of the methods selects parameters of the stimulation protocol for each patient, using a model of lower urinary tract function involving coupled nonlinear oscillators.
Treatments for various infirmities sometime require the destruction of otherwise healthy tissue in order to produce a beneficial effect. Malfunctioning tissue is identified and then lesioned or otherwise compromised in order to produce a beneficial outcome, rather than attempting to repair the tissue to its normal functionality. A variety of techniques and mechanisms have been designed to produce focused lesions directly in target nerve tissue, but collateral damage is inevitable.
Other treatments for malfunctioning tissue can be medicinal in nature, but in many cases the patients become dependent upon artificially synthesized chemicals. In many cases, these medicinal approaches have side effects that are either unknown or quite significant. Unfortunately, the beneficial outcomes of surgery and medicines are often realized at the cost of function of other tissues, or risks of side effects.
The use of electrical stimulation for treatment of medical conditions has been well known in the art for nearly two thousand years. It has been recognized that electrical stimulation of the brain and/or the peripheral nervous system and/or direct stimulation of the malfunctioning tissue holds significant promise for the treatment of many ailments, because such stimulation is generally a wholly reversible and non-destructive treatment.
Nerve stimulation is thought to be accomplished directly or indirectly by depolarizing a nerve membrane, causing the discharge of an action potential; or by hyperpolarization of a nerve membrane, preventing the discharge of an action potential. Such stimulation may occur after electrical energy, or also other forms of energy, are transmitted to the vicinity of a nerve [F. RATTAY. The basic mechanism for the electrical stimulation of the nervous system. Neuroscience 89 (2, 1999):335-346; Thomas HEIMBURG and Andrew D. Jackson. On soliton propagation in biomembranes and nerves. PNAS 102 (28, 2005): 9790-9795]. Nerve stimulation may be measured directly as an increase, decrease, or modulation of the activity of nerve fibers, or it may be inferred from the physiological effects that follow the transmission of energy to the nerve fibers.
One of the most successful applications of modern understanding of the electrophysiological relationship between muscle and nerves is the cardiac pacemaker. Although origins of the cardiac pacemaker extend back into the 1800's, it was not until 1950 that the first practical, albeit external and bulky, pacemaker was developed. The first truly functional, wearable pacemaker appeared in 1957, and in 1960, the first fully implantable pacemaker was developed.
Around this time, it was also found that electrical leads could be connected to the heart through veins, which eliminated the need to open the chest cavity and attach the lead to the heart wall. In 1975 the introduction of the lithium-iodide battery prolonged the battery life of a pacemaker from a few months to more than a decade. The modern pacemaker can treat a variety of different signaling pathologies in the cardiac muscle, and can serve as a defibrillator as well (see U.S. Pat. No. 6,738,667 to DENO, et al., the disclosure of which is incorporated herein by reference).
Another application of electrical stimulation of nerves has been the treatment of radiating pain in the lower extremities by stimulating the sacral nerve roots at the bottom of the spinal cord (see U.S. Pat. No. 6,871,099 to WHITEHURST, et al., the disclosure of which is incorporated herein by reference).
Many such therapeutic applications of electrical stimulation involve the surgical implantation of electrodes within a patient. In contrast, for embodiments of the present invention, the disclosed devices and medical procedures stimulate nerves by transmitting energy to nerves and tissue non-invasively. They may offer the patient an alternative that does not involve surgery. A medical procedure is defined as being non-invasive when no break in the skin (or other surface of the body, such as a wound bed) is created through use of the method, and when there is no contact with an internal body cavity beyond a body orifice (e.g., beyond the mouth or beyond the external auditory meatus of the ear). Such non-invasive procedures are distinguished from invasive procedures (including minimally invasive procedures) in that invasive procedures do involve inserting a substance or device into or through the skin or into an internal body cavity beyond a body orifice. For example, transcutaneous electrical nerve stimulation (TENS) is non-invasive because it involves attaching electrodes to the surface of the skin (or using a form-fitting conductive garment) without breaking the skin. In contrast, percutaneous electrical stimulation of a nerve is minimally invasive because it involves the introduction of an electrode under the skin, via needle-puncture of the skin (see commonly assigned co-pending US Patent Application 2010/0241188, entitled Percutaneous Electrical Treatment of Tissue to ERRICO et al, which is hereby incorporated by reference in its entirety).
Potential advantages of non-invasive medical methods and devices relative to comparable invasive procedures are as follows. The patient may be more psychologically prepared to experience a procedure that is non-invasive and may therefore be more cooperative, resulting in a better outcome. Non-invasive procedures may avoid damage of biological tissues, such as that due to bleeding, infection, skin or internal organ injury, blood vessel injury, and vein or lung blood clotting. Non-invasive procedures generally present fewer problems with biocompatibility. In cases involving the attachment of electrodes, non-invasive methods have less of a tendency for breakage of leads, and the electrodes can be easily repositioned if necessary. Non-invasive methods are sometimes painless or only minimally painful and may be performed without the need for even local anesthesia. Less training may be required for use of non-invasive procedures by medical professionals. In view of the reduced risk ordinarily associated with non-invasive procedures, some such procedures may be suitable for use by the patient or family members at home or by first-responders at home or at a workplace, and the cost of non-invasive procedures may be reduced relative to comparable invasive procedures.
Electrodes that are applied non-invasively to the surface of the body have a long history, including electrodes that were used to stimulate underlying nerves [L. A. GEDDES. Historical Evolution of Circuit Models for the Electrode-Electrolyte Interface. Annals of Biomedical Engineering 25 (1997):1-14]. However, electrical stimulation of nerves in general fell into disfavor in middle of the twentieth century, until the “gate theory of pain” was introduced by Melzack and Wall in 1965. This theory, along with advances in electronics, reawakened interest in the use of implanted electrodes to stimulate nerves, initially to control pain. Screening procedures were then developed to determine suitable candidates for electrode implantation, which involved first determining whether the patient responded when stimulated with electrodes applied to the surface of the body in the vicinity of the possible implant. It was subsequently found that the surface stimulation often controlled pain so well that there was no need to implant a stimulating electrode [Charles BURTON and Donald D. Maurer. Pain Suppression by Transcutaneous Electronic Stimulation. IEEE Transactions on Biomedical Engineering BME-21(2, 1974): 81-88].
Non-invasive transcutaneous electrical nerve stimulation (TENS) was then developed for treating different types of pain, including pain in a joint or lower back, cancer pain, post-operative pain, post-traumatic pain, and pain associated with labor and delivery [Steven E. ABRAM. Transcutaneous Electrical Nerve Stimulation. pp 1-10 in: Joel B. Myklebust, ed. Neural stimulation (Volume 2). Boca Raton, Fla. CRC Press 1985; WALSH D M, Lowe A S, McCormack K. Willer J-C, Baxter G D, Allen J M. Transcutaneous electrical nerve stimulation: effect on peripheral nerve conduction, mechanical pain threshold, and tactile threshold in humans. Arch Phys Med Rehabil 79 (1998):1051-1058; J A CAMPBELL. A critical appraisal of the electrical output characteristics of ten transcutaneous nerve stimulators. Clin. phys. Physiol. Meas. 3(2, 1982): 141-150; U.S. Pat. No. 3,817,254, entitled Transcutaneous stimulator and stimulation method, to Maurer; U.S. Pat. No. 4,324,253, entitled Transcutaneous pain control and/or muscle stimulating apparatus, to Greene et al; U.S. Pat. No. 4,503,863, entitled Method and apparatus for transcutaneous electrical stimulation, to Katims; U.S. Pat. No. 5,052,391, entitled High frequency high intensity transcutaneous electrical nerve stimulator and method of treatment, to Silberstone et al; U.S. Pat. No. 6,351,674, entitled Method for inducing electroanesthesia using high frequency, high intensity transcutaneous electrical nerve stimulation, to Silverstone].
As TENS was being developed to treat pain, non-invasive electrical stimulation using surface electrodes was simultaneously developed for additional therapeutic or diagnostic purposes, which are known collectively as electrotherapy. Neuromuscular electrical stimulation (NMES) stimulates normally innervated muscle in an effort to augment strength and endurance of normal (e.g., athletic) or damaged (e.g., spastic) muscle. Functional electrical stimulation (FES) is used to activate nerves innervating muscle affected by paralysis resulting from spinal cord injury, head injury, stroke and other neurological disorders, or muscle affected by foot drop and gait disorders. FES is also used to stimulate muscle as an orthotic substitute, e.g., replace a brace or support in scoliosis management. Another application of surface electrical stimulation is chest-to-back stimulation of tissue, such as emergency defibrillation and cardiac pacing. Surface electrical stimulation has also been used to repair tissue, by increasing circulation through vasodilation, by controlling edema, by healing wounds, and by inducing bone growth. Surface electrical stimulation is also used for iontophoresis, in which electrical currents drive electrically charged drugs or other ions into the skin, usually to treat inflammation and pain, arthritis, wounds or scars.
Stimulation with surface electrodes is also used to evoke a response for diagnostic purposes, for example in peripheral nerve stimulation (PNS) that evaluates the ability of motor and sensory nerves to conduct and produce reflexes. Surface electrical stimulation is also used in electroconvulsive therapy to treat psychiatric disorders; electroanesthesia, for example, to prevent pain from dental procedures; and electrotactile speech processing to convert sound into tactile sensation for the hearing impaired. All of the above-mentioned applications of surface electrode stimulation are intended not to damage the patient, but if higher currents are used with special electrodes, electrosurgery may be performed as a means to cut, coagulate, desiccate, or fulgurate tissue [Mark R. PRAUSNITZ. The effects of electric current applied to skin: A review for transdermal drug delivery. Advanced Drug Delivery Reviews 18 (1996) 395-425].
Another form of non-invasive electrical stimulation is magnetic stimulation. It involves the induction, by a time-varying magnetic field, of electrical fields and current within tissue, in accordance with Faraday's law of induction. Magnetic stimulation is non-invasive because the magnetic field is produced by passing a time-varying current through a coil positioned outside the body, inducing at a distance an electric field and electric current within electrically-conducting bodily tissue. The electrical circuits for magnetic stimulators are generally complex and expensive and use a high current impulse generator that may produce discharge currents of 5,000 amps or more, which is passed through the stimulator coil to produce a magnetic pulse. The principles of electrical nerve stimulation using a magnetic stimulator, along with descriptions of medical applications of magnetic stimulation, are reviewed in: Chris HOVEY and Reza Jalinous, The Guide to Magnetic Stimulation, The Magstim Company Ltd, Spring Gardens, Whitland, Carmarthenshire, SA34 0HR, United Kingdom, 2006.
Despite its attractiveness, non-invasive electrical stimulation of a nerve is not always possible or practical. This is primarily because the current state of the art may not be able to stimulate a deep nerve selectively or without producing excessive pain, because the stimulation may unintentionally stimulate nerves other than the nerve of interest, including nerves that cause pain. For this reason, forms of electrical stimulation other than TENS may be best suited for the treatment of particular types of pain [Paul F. WHITE, Shitong Li and Jen W. Chiu. Electroanalgesia: Its Role in Acute and Chronic Pain Management. Anesth Analg 92 (2001):505-13]. Accordingly, there remains a long-felt but unsolved need to stimulate nerves totally non-invasively, selectively, and essentially without producing pain.
As compared with what would be experienced by a patient undergoing non-invasive stimulation with conventional TENS or magnetic stimulation methods, an objective of the stimulators disclosed here is to produce relatively little pain for a given depth of stimulus penetration, but nevertheless to stimulate the target nerve to achieve therapeutic results. Or conversely, for a given amount of pain or discomfort on the part of the patient (e.g., the threshold at which such discomfort or pain begins), an objective of the present invention is to achieve a greater depth of penetration or power of the stimulus under the skin. When some nerves are stimulated electrically, they may produce undesirable responses in addition to the therapeutic effect that is intended. For example, the stimulated nerves may produce unwanted muscle twitches. It is therefore another objective of the present invention to selectively produce only the intended therapeutic effect when the target nerve is stimulated by the disclosed devices.
Non-invasive capacitive stimulating electrodes, which contact the patient's skin with a dielectric material, may produce more uniform current densities than electrodes made of electrically conducting material. Their use may therefore be advantageous as a method to avoid potential pain when a patient is electrically stimulated. However, previous capacitive stimulating electrodes have required the use of a high voltage power supply, which is accompanied by the inherent danger of high voltage breakdowns of the electrode's dielectric material [L. A. GEDDES, M. Hinds, and K. S. Foster. Stimulation with capacitor electrodes. Medical and Biological Engineering and Computing 25 (1987): 359-360; Thierry KELLER and Andreas Kuhn. Electrodes for transcutaneous (surface) electrical stimulation. Journal of Automatic Control, University of Belgrade 18(2, 2008):35-45; U.S. Pat. No. 3,077,884, entitled Electro-physiotherapy apparatus, to BARTROW et al, and U.S. Pat. No. 4,144,893, entitled Neuromuscular therapy device, to HICKEY]. Therefore, another objective of one embodiment of the present invention to devise a capacitive stimulating device that does not require the use of a high voltage power supply.
The present invention uses electrical nerve stimulation to treat overactive bladder and urinary incontinence, particularly non-invasive, transcutaneous electrical stimulation of the posterior tibial nerve at a location near the patient's ankle. The storage and voiding of urine are performed by the urinary bladder and urethra, which are muscular structures controlled by the nervous system. Individuals with an overactive bladder exhibit a sudden urge to urinate and a high frequency of urination. They often, but not always, also exhibit urge incontinence that is associated with the leakage of urine due to bladder muscles that contract or spasm inappropriately and/or with dysfunction of urethral sphincters that would normally prevent the passage of urine.
The prevalence of overactive bladder is approximately 11-19% in men and 13-17% in women, which increases with age. In the year 2000, the costs in the United States of urinary incontinence and overactive bladder were estimated to be 19.5 and 12.6 billion dollars, respectively, taking into account costs associated with diagnosis and treatment, as well as consequent costs such as predisposition to urinary tract infections, ulcers, perineal rashes and other skin conditions, infections, falls and broken bones, and premature nursing home admissions. Psychologically, overactive bladder and incontinence are associated with embarrassment, isolation, stigmatization, depression, and the fear of institutionalization [TYAGI 5, Thomas C A, Hayashi Y, Chancellor M B. The overactive bladder: Epidemiology and morbidity. Urol Clin North Am. 33(4, 2006): 433-8; HU T W, Wagner T H, Bentkover J D, Leblanc K, Zhou S Z, Hunt T. Costs of urinary incontinence and overactive bladder in the United States: a comparative study. Urology. 63(3, 2004): 461-465].
Management options for overactive bladder include lifestyle adjustments, bladder retraining, pelvic floor exercises, biofeedback, and pharmacotherapy. Anticholinergic medications are the mainstay of treatment. However, side effects and urinary retention occur in approximately 20% of those who use these medications. In other patients, the medications are ineffective, such that 75% of patients discontinue the use of anticholinergic medications within one year. Major surgical procedures for overactive bladder are considered last resorts, as they potentially lead to serious side effects. Having failed conservative and drug-based therapies for incontinence, some patients resign themselves to a lifetime of containment devices and pads, rather than resort to surgery [Victor W. NITTI and Jerry G. Blaivas. Urinary Incontinence: Epidemiology, Pathophysiology, Evaluation, and Management Overview. Chapter 60 In: Campbell-Walsh Urology, 9th ed., A J Wein, L R Kavoussi, A C Novick, A W Partin and C A Peters, eds. Philadelphia, Pa.: Saunders Elsevier; 2007. pp 2046-2078; LENTZ G M. Urogynecology: physiology of micturition, diagnosis of voiding dysfunction, and incontinence: surgical and nonsurgical treatment. In: Katz V L, Lentz G M, Lobo R A, Gershenson D M, eds. Comprehensive Gynecology. 5th ed. Philadelphia, Pa.: Mosby Elsevier; 2007: chap 21, pp. 537-568].
If pharmacotherapy is unsuccessful and surgery is not being considered, patients with an overactive bladder or incontinence are increasingly treated by neuromodulation [VAN BALKEN M R, Vergunst H, Bemelmans B L. The use of electrical devices for the treatment of bladder dysfunction: a review of methods. J. Urol. 172(3, 2004):846-51; Sandip P. VASAVADA and Raymond R. Rackley. Electrical stimulation for storage and emptying disorders. Chapter 64 in Campbell-Walsh Urology, 9th ed., A J Wein, L R Kavoussi, A C Novick, A W Partin and C A Peters, eds. Philadelphia, Pa.: Saunders Elsevier; 2007. pp 2147-2167; YAMANISHI T, Kama T, Yoshida K I. Neuromodulation for the treatment of urinary incontinence. Int J Urol 15 (2008):665-672]. Sacral nerve electrical stimulation is currently the most common form of neuromodulation that is used to treat overactive bladder and incontinence, which requires an incision and placement of electrodes in the sacrum, in the lower portion of the patient's spine. The procedure is expensive, and problems arise in up to a third of the patients, including change in bowel function, infection, lead movement, pain at implant sites, and/or unpleasant stimulation or sensation.
Percutaneous tibial nerve stimulation (PTNS, also known as posterior tibial nerve stimulation) offers a safer, less invasive treatment alternative for overactive bladder than sacral nerve neuromodulation. Rather than requiring an incision and placement of electrodes in the sacrum, PTNS stimulates sacral nerve roots a location much closer to the surface of the skin, by stimulating the posterior tibial nerve slightly above the ankle. To perform PTNS, a needle is inserted temporarily through the skin to allow introduction of an electrode that will stimulate tibial nerve at that location. However, this procedure may cause problems associated with needle insertion, and because significant training is required in order to perform PTNS, it must ordinarily be performed by professionals in an office setting.
Noninvasive PTNS can also be performed with surface electrodes, wherein the posterior tibial nerve is stimulated transcutaneously. This eliminates potential problems associated with needle insertion and reduces training requirements, such that the patient can sometimes perform the stimulation at home. However, the use of surface electrodes exacerbates the potential for pain from the electrical stimulation itself. This is because transcutaneous PTNS as it is currently performed is unable to stimulate the tibial nerve selectively, potentially causing pain through the stimulation of nearby tissue and other nerves, and because the tibial nerve itself can sense pain if the stimulation waveform is not properly designed. Accordingly, the electrical stimulus power must be limited to what is less than the threshold of pain from surrounding tissue and the tibial nerve itself, which in turn limits the ability of transcutaneous tibial nerve stimulation as it is currently performed to excite portions of the nervous system that may prevent or delay episodes of overactive bladder and urge incontinence. A related selectivity problem is that tibial nerve stimulation will induce movements and contractions of muscle in the toes and foot, such that the electrical stimulus power must also be limited to what is less than the threshold for such movement, thereby limiting the stimulus power that could otherwise be used to treat overactive bladder and urge incontinence.
An objective of the present invention is therefore to devise stimulation devices that are able to deliver higher electrical currents to nerves such as the posterior tibial nerve, selectively and noninvasively, without causing pain, and without inducing muscle movement, through a novel architecture and arrangement of electrodes within the devices, as well as through novel stimulation waveforms. The present invention also discloses a novel magnetic stimulator that may be applied to nerves such as the posterior tibial nerve. The magnetic stimulator has an architecture and stimulation waveforms that share features with the disclosed electrode-based stimulation devices.
Another aspect of the present invention is that it treats overactive bladder, incontinence, and/or related urological disorders through a novel method and mechanism that is based in part upon a particular theory for the origin of overactive bladder and urge incontinence. Currently, the best-known theories are the following four: myogenic, neurogenic, afferent, and integrative or autonomous [Henderson E, Drake M. Overactive bladder. Maturitas. 2010 66(3, 2010):257-62; En MENG. Recent research advances in the pathophysiology of overactive bladder. Incont Pelvic Floor Dysfunct 3(Suppl 1, 2009): 5-7]. Unlike previous methods of neuromodulation for treating overactive bladder, the presently disclosed methods are based in part upon the integrative or autonomous theory, which attributes bladder muscle instability to abnormal synchronization and imbalanced excitation/inhibition of contractile modules within the bladder, each module of which may contain intramural ganglia and interstitial cells. According to the disclosed methods, the bladder modules may be represented as coupled nonlinear oscillators, leading to a characterization of the dynamics and treatment of the bladder in terms of predictable thresholds that separate different qualitatively different types of bladder dynamics. Implementation of the disclosed methods is intended to aid in evaluating whether an individual is a suitable candidate for the tibial nerve stimulation, in the selection of parameters for the electrical stimulation protocol, and in evaluating the extent to which the stimulation has had an effect.